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VERTEX PHARMACEUTICALS INCORPORATED

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A Letter from our Executive Chairman and Chief Executive Officer

Dear Shareholders:

20222023 was an outstandinga transformative year for Vertex. We secured more reimbursement agreements and served more people withextended our leadership in cystic fibrosis (“CF”) than, expanded into new disease areas with CASGEVY regulatory approvals and commercial launches for severe sickle cell disease (“SCD”) and transfusion-dependent beta thalassemia (“TDT”) in any previous year. Ourmultiple regions, and continued the rapid advancement of our broad pipeline, which offers the potential for multiple commercial launch opportunities in disease areas outside of CF over the next few years. We believe that these important advances in 2023, combined with our continued excellent financial performance, fuel a new era of medical and commercial diversification for Vertex and significant value creation for patients and shareholders alike.

Net product revenues from our CF medicines grew to $9.87 billion in 2023, representing an 11% increase from 2022. We continued to invest significantly in innovation — both internal and external — to support our differentiated research and development (“R&D”) strategy, which focusesapproach, focused on validated targets that address causal human biology, predictive assaysbiomarkers that translate from bench to bedside, efficient development and biomarkers, rapid paths to approval,regulatory pathways, and product candidates with transformative potential, drove substantial advancement of our pipeline. We alsopotential. Our differentiated R&D strategy has continued to strengthendeliver. We have obtained approvals for the first CRISPR/Cas9 gene-edited cell therapy in the world for the treatment of SCD and TDT and we have also delivered positive Phase 3 results for VX-548, our financial profile. These important advancesnovel NaV1.8 pain signal inhibitor in 2022 lay the foundationacute pain, and for sustained leadershipour triple combination of vanzacaftor/tezacaftor/deutivacaftor in CF, multiple near term global commercial launches outside of CF, and significant value creation for patients and shareholders for many years to come.

Net product revenues from our CF franchise grew to $8.9 billionCF. Our programs in 2022, representing an 18% increase from 2021, and a near tripling of revenues since 2018. We continued to invest significantly in both internal and external innovation in support of our differentiated R&D approach, which has leveraged serial innovation to produce four transformational medicines for patients with CF and has now delivered assets into the clinic across eight disease areas and multiple modalities. Numerous programs, including in CF, sickle cell disease, beta thalassemia, acuteneuropathic pain, APOL1-mediated kidney disease, and type 1 diabetes are pasthave all passed the proof-of-concept stage and represent additional multi-billion-dollar market potential. In total, our clinical-stage pipeline now spans 10 disease areas and multiple assets hold the potential for near-term commercialization.modalities, including small molecules, oligonucleotides, and cell and genetic therapies.

Our CF franchise exemplifies the patient impactAlong with developing and financial success that can be achieved through our business model and R&D strategy. Broad reimbursement and access to ourcommercializing transformative medicines is now available in over 40 countries and, in 2022, we treated morefor people with CF than ever before. We reached lower age groups with the successful launches of TRIKAFTA/KAFTRIO in Europe and Canada for children with CF aged 6serious diseases, we continue to 11 years and of ORKAMBI in the U.S. for children with CF aged 1 to 2 years, which helped generate another year of double-digit revenue growth. In addition, we submitted U.S. and European regulatory filings for TRIKAFTA/KAFTRIO in children with CF aged 2 to 5 years and for KALYDECO in 1- to 4-month-old infants with CF. We also continued our strategy of serial innovation by completing enrollment of the Phase 3 trials of our triple combination of vanzacaftor/tezacaftor/deutivacaftor; entering the clinic with a messenger RNA therapeutic designed for the estimated 5,000 people with CF who cannot benefit from our current medicines; and advancing multiple next generation potentiators and correctors that have the potential to deliver even greater benefits to people living with CF.

Beyond CF, our differentiated R&D strategy has delivered a broad, deep and advanced pipeline with multiple potentially transformative mid- and late-stage assets, each representing multi-billion dollar market opportunities.

	In sickle cell disease and transfusion dependent beta thalassemia, we completed the European Union and U.K. regulatory submissions for exa-cel, a one-time gene therapy that has the potential to be a functional cure for people living with these diseases. Both submissions have been validated by the respective regulatory agencies. We also initiated a rolling regulatory submission in the U.S., which we recently completed. In addition, our teams made meaningful progress in pre-launch preparation, and in establishing the infrastructure necessary to ensure patient access to this therapy.
	In pain, we announced positive Phase 2 results for VX-548 in acute pain and initiated Phase 3 studies, while also initiating a Phase 2 study in chronic neuropathic pain. Pre-launch preparations for acute pain are underway.
	In APOL1-mediated kidney disease, we commenced pivotal clinical development of inaxaplin and obtained breakthrough therapy and PRIME designations in the U.S. and European Union, respectively.

In type 1 diabetes, we achieved proof-of-concept for our VX-880 stem-cell-derived islet cell therapy program and continued to enroll patients in the ongoing Phase 1/2 clinical trial. In addition, we progressed our VX-264 program, in which the cells are encapsulated in an immunoprotective device, into the clinic, while also continuing pre-clinical development for our hypoimmune VX-880 cell program. Furthermore, we completed the acquisition of ViaCyte, Inc., a company focused on stem-cell-derived cell replacement therapies for type 1 diabetes with complementary assets, capabilities, and technologies that we believe will accelerate our current programs to bring forward a functional cure for the disease.

In alpha-1 antitrypsin (“AAT”) deficiency, we initiated a first-in-human clinical trial for VX-634, the first in a series of next-wave AAT correctors with significantly improved potency and drug-like properties compared to our prior AAT correctors. We also initiated a second Phase 2 study of VX-864, a first-generation AAT corrector, to assess the impact of longer-term treatment on the liver and on levels of functional AAT in the plasma.

In addition to our focus on discovering transformative medicines and growing our business, we remained committed to supportingsupport patients, our local communities, and our workforce, and progressed our environmental, social, and governance practices. We advanced our progress in 2022 by continuing to integrate sustainability best practices in our operations, exceeding our environmental targets, and making a positive impact in the communities where we live and work. We alsoemployees. Last year, Vertex celebrated the 5its 15^th anniversaryGlobal Day of Service, with participation by 60% of employees contributing nearly 8,300 hours of volunteer work across more than 125 projects with 73 non-profit groups. In addition, Vertex and the Vertex Foundation which works to improve the lives of people with serious diseases and contribute to our local communities,provided more than $42 million in charitable donations, with a focus on education, innovation, health, and health. our local communities. We remain committed to recruiting, retaining, and developing highly talented employees from a diverse range of backgrounds, promoting our employees’ continued well-being and professional development, and nurturing our unique culture, which has enabled us to deliver multiple transformative medicines to patients. Our efforts continue to be recognized externally, and in 2023, Vertex was named to Fortune 100 Best Companies to Work For^® 2023, Forbes Best Employers for Diversity 2023, and 2023 PEOPLE^® Companies that Care.

In 2022,summary, consistent execution of our R&D and corporate strategy continues to deliver strong and durable financial results, setting up significant and sustainable long-term growth for the business. We are treating more people with CF around the world and are working to translate the historic regulatory approvals for CASGEVY in SCD and TDT into real world patient benefit. We are also preparing for additional potential near-term submissions, approvals, and launches, including for vanzacaftor/tezacaftor/deutivacaftor in CF and VX-548 in acute pain, both of which have the potential to dramatically improve patient lives and represent significant opportunities for Vertex. In parallel, we are progressing the next wave of innovation and look forward to bringing additional first-in-class or best-in-class medicines to people living with serious diseases. This is an extraordinarily exciting time for Vertex and, the Vertex Foundation contributed nearly $35 million in charitable giving to local communities globally. Our employees also continued to participate in community service throughout the year, with 57% of Vertexians participating in our global Day of Service, which resulted in more than 6,300 hours of volunteer work across 90 projects in 20 countries. We also continued to nurture our culture, focus on the well-being of our people, and develop our talent, all while successfully transitioning to a hybrid work environment.

Asas Executive Chairman and Chief Executive Officer, we are committed to the continued successful execution of our strategy of serial innovation that will be criticalstrategy to our long-term success in bringing more transformative medicines to patients. Looking todrive exceptional results for patients, the future, we are focused on sustaining and expanding our leadership in CF, preparing for multiple new product launches outside of CF, bringing the next wave of innovation to patients, and continuing to deliver revenue growth and industry-leading operating margins. We believe our focus on transforming and curing serious diseases, combined with the experience and passion of our workforcemedical community, and our strong financial profile, will fuel our continued success for both patients and shareholders in 2023 and beyond.shareholders.

Sincerely,

Sincerely, Jeffrey M. Leiden, M.D., Ph.D. Executive Chairman		Reshma Kewalramani, M.D. Chief Executive Officer and President

Notice of Annual Meeting of Shareholders

Wednesday, May 17, 2023 9:00 a.m. (Eastern Time) https://meetnow.global/MSC2Z5F Notice of Annual Meeting of Shareholders Wednesday, May 15, 2024 9:00 a.m. (Eastern Time) https://meetnow.global/MQ4XFU9 Dear Shareholders: You are invited to attend the Vertex Pharmaceuticals Incorporated 2024 Annual Meeting of Shareholders. At the annual meeting, shareholders will vote:   Dear Shareholders: You are invited to attend the Vertex Pharmaceuticals Incorporated 2023 Annual Meeting of Shareholders. At the annual meeting, shareholders will vote:

	to elect the nineeleven director nominees that are set forth in the attached proxy statement to our board of directors to serve for a one-year term until the 20242025 annual meeting of shareholders and until such person’s successor has been duly elected and qualified;
	to ratify the selection of Ernst & Young LLP as our independent registered public accounting firm for 2023;2024;
	to hold an advisory vote on our 20222023 named executive officer compensation; and
	to hold an advisory vote on two proposals submitted by our shareholders, if properly presented at the frequency of future advisory votes on our executive compensation.
Shareholders also will transact any other business that may properly come before the annual meeting or any adjournment or postponement of the annual meeting. MEETING INFORMATION. PROXY MATERIALS: We are using the “Notice and Access” method of providing proxy materials to you via the Internet. We are mailing to you a Notice of Internet Availability of Proxy Materials instead of paper copies of this notice, our proxy statement, and our Annual Report on Form 10-K for the year ended December 31, 2022 (“Annual Report”). Notice and Access provides a convenient way for you to access our proxy materials. The Notice of Internet Availability of Proxy Materials includes instructions on how to access this notice, our proxy statement, and our Annual Report and how to vote your shares. The Notice of Internet Availability of Proxy Materials also contains instructions on how to receive a paper copy of the proxy materials and our Annual Report, if you prefer. MEETING ACCESS: THE ANNUAL MEETING WILL BE HELD VIRTUALLY VIA WEBCAST. A VIRTUAL MEETING WILL FACILITATE SHAREHOLDER ATTENDANCE AND PARTICIPATION BY ENABLING SHAREHOLDERS TO PARTICIPATE FROM ANY LOCATION AND AT NO COST. YOU WILL BE ABLE TO PARTICIPATE IN THE MEETING ONLINE, VOTE YOUR SHARES ELECTRONICALLY, AND SUBMIT YOUR QUESTIONS DURING THE MEETING BY VISITING HTTPS://MEETNOW.GLOBAL/MSC2Z5F. THERE IS NO PHYSICAL LOCATION FOR THE ANNUAL MEETING. Shareholders will need their unique control number, which appears on the Notice of Internet Availability of Proxy Materials or proxy card (printed in the shaded bar), or within the body of the email sending the proxy statement. If you hold shares beneficially through a bank, broker or other nominee (that is, in “street name”), you must register in advance to gain access to the virtual meeting and to vote shares electronically during the meeting. To register, you will need to obtain a legal proxy from your bank, broker or other nominee. Once you

Shareholders also will transact any other business that may properly come before the annual meeting or any adjournment or postponement of the annual meeting.

MEETING INFORMATION

PROXY MATERIALS:

We are using the “Notice and Access” method of providing proxy materials to you via the Internet. We are mailing to you a Notice of Internet Availability of Proxy Materials instead of paper copies of this notice, our proxy statement, and our Annual Report on Form 10-K for the year ended December 31, 2023 (“Annual Report”). Notice and Access provides a convenient way for you to access our proxy materials. The Notice of Internet Availability of Proxy Materials includes instructions on how to access this notice, our proxy statement, and our Annual Report and how to vote your shares. The Notice of Internet Availability of Proxy Materials also contains instructions on how to receive a paper copy of the proxy materials and our Annual Report, if you prefer.

MEETING ACCESS:

THE ANNUAL MEETING WILL BE HELD VIRTUALLY VIA WEBCAST. A VIRTUAL ANNUAL MEETING WILL FACILITATE SHAREHOLDER ATTENDANCE AND PARTICIPATION BY ENABLING SHAREHOLDERS TO PARTICIPATE FROM ANY LOCATION AND AT NO COST. YOU WILL BE ABLE TO PARTICIPATE IN THE MEETING ONLINE, VOTE YOUR SHARES ELECTRONICALLY, AND SUBMIT YOUR QUESTIONS DURING THE MEETING BY VISITING HTTPS://MEETNOW.GLOBAL/MQ4XFU9. THERE IS NO PHYSICAL LOCATION FOR THE ANNUAL MEETING.

Shareholders will need their unique control number, which appears on the Notice of Internet Availability of Proxy Materials or proxy card (printed in the shaded bar), or within the body of the email sending the proxy statement. If you hold shares beneficially through a bank, broker or other nominee (that is, in “street name”), you must register in advance to gain access to the virtual meeting and to vote shares electronically during the meeting.

SUMMARY

 

Our CF net product revenues increased to $8.93 billion 2023 was a transformational year for the company marked by significant advances in 2022, up 18% or approximately $1.4 billion, from our 2021 net product revenues.

Our total R&D, acquired in-process research, and development (“AIPR&D”) and selling, general and administrative (“SG&A”) expenses decreased to $3.6 billion compared to $3.9 billion in 2021. The decrease was primarily due to lower AIPR&D as a result of the one-time $900 million upfront payment to CRISPR Therapeutics AG (“CRISPR”) in 2021, partially offset by increased investment in support of multiple programs that have advanced to mid- and late-stage clinical development, and commercialization, across the costsentire company. Our strategy of investing in scientific innovation to support launchescreate transformative medicines for people with serious diseases, with a focus on specialty markets, is delivering. Not only did we extend our leadership in cystic fibrosis (“CF”) by reaching more people with CF than ever before, but we also diversified commercially with the launch of Vertex’s therapies globally.

VERTEX PHARMACEUTICALS INCORPORATED - 2023 Proxy Statement    7

Marketed Products

Our successful strategy of serial innovation has sustained and expanded our leadership position in CF and continues to propel us toward our goal of delivering highly effective treatments to all patients with CF. In January 2012, KALYDECO was first approved to treat approximately 1,000 patients with the G551D mutation in the U.S. Since then, we have focused on expanding the number of patients eligible for our medicines, expanding access to our medicines in additional geographies, and seeking improved treatment options for all patients with CF.

Our four approved medicines have broad reimbursement, are accessible in more than 40 countries, and are being used to treat more than two-thirds of the approximately 88,000 people with CF in North America, Europe, and Australia. Yet, as of the beginning of the year, there were more than 25,000 untreated patients in these geographies who could benefit from our therapies. We expect to grow our CF business with (i) continued uptake by patients in countries where we are early on the launch curve, such as those with recently achieved reimbursement agreements, (ii) label expansions, including into younger patient groups, (iii) the development of mRNA therapies for people with CF who are not eligible for our approved CFTR modulators, and (iv) growth in the number of people living with CF.

Since the beginning of 2022, notable progress includes:

	The European Commission and the Medicines and Healthcare products Regulatory Agency (“MHRA”) granted marketing authorization for KAFTRIOCASGEVY, our gene-edited cell therapy for the treatment of children with CF 6 through 11 years of age who have at least one F508del mutation in the CFTR gene.
	Health Canada granted marketing authorization for TRIKAFTA for children with CF 6 through 11 years of age who have at least one F508del mutation.
	The U.S. Food and Drug Administration (“FDA”) approved the use of ORKAMBI for children with CF 12 to less than 24 months of age who are homozygous for the F508del mutation.
	We submitted global regulatory filings for TRIKAFTA/KAFTRIO in children with CF 2 through 5 years of age and for KALYDECO in children with CF from 1 month to less than 4 months of age.

Potential Near-Term Launch Opportunities

We are preparing for the following near-term launches of new products:

	Exa-cel in severe sickle cell disease (“SCD”) and transfusion-dependent beta thalassemia (“TDT”). We completed European UnionIn addition, we substantially progressed our broad and U.K. regulatory submissionsdiverse pipeline, prepared for exagamglogene autotemcel (“exa-cel”), an ex-vivo CRISPR gene-editing therapy,additional potential near-term launch opportunities in the fourth quarter of 2022CF and initiated a rolling submission in the U.S., which we recently completed. The European Medicines Agency (“EMA”) and MHRA have validated the exa-cel marketing authorization application (“MAA”) for their respective jurisdictions.
	VX-548 in acute pain. We continue to enroll the Phase 3 pivotal program for VX-548 for the treatment of moderate to severe acute pain, and further strengthened our financial profile. Today, our CF medicines are collectively being used to treat nearly three-quarters of the approximately 92,000 people with CF in North America, Europe and Australia. Our CF medicines are used by people in over 60 countries, and TRIKAFTA/KAFTRIO is now reimbursed or accessible in more than 40 of those countries. As we look to the future, we expect to complete thecontinue to grow our CF business through label expansions, approvals of new medicines and expanded reimbursement. We also continue to serially innovate in CF, as demonstrated by our recent announcement of positive data from three pivotal program in late 2023 or early 2024.
	Vanzacaftor/tezacaftor/deutivacaftor, the next-in-class triple combination, in CF. We continuedstudies evaluating our strategy of serial innovation by completing enrollment of the Phase 3 trials of our once-dailynext-generation triple combination of vanzacaftor/tezacaftor/deutivacaftor. Our clinical and preclinical data indicate that the vanzacaftor/tezacaftor/deutivacaftor (the “vanzacaftor triple”). This new triple combination regimen has demonstrated the potential to provide enhanced benefit beyond TRIKAFTA/KAFTRIO for people who have at least one mutation in their CFTR gene responsive to CFTR modulators. This regimenclinical benefits over and above TRIKAFTA, and also has the benefitadvantages of a once-daily dosing regimen and has substantially decreased royalties compared with TRIKAFTA.

VERTEX PHARMACEUTICALS INCORPORATED - 2023 Proxy Statement    8

Research and Development

We invest in research and development to discover and develop transformative medicines for people with serious diseases, with a focus on specialty markets. Our research and development strategy combines transformative advances in the understanding of human disease and the science of therapeutics to dramatically advance human health. This approach has yielded a broad and deep pipeline and increases the speed and likelihood of successfully bringing medicines to patients, as demonstrated by our success in moving novel product candidates into clinical trials and obtaining marketing approvals, including for TRIKAFTA/KAFTRIO, SYMDEKO/SYMKEVI, ORKAMBI, and KALYDECO for the treatment of CF. The strategy was designed to deliver transformative medicines for serious diseases at high rates of success, and it has delivered just that. Beyond CF, our approach to drug discovery has yielded clinical proof-of-concept in five additional disease areas: SCD and beta thalassemia with exa-cel, acute pain with VX-548, APOL1-mediated kidney disease (“AMKD”) with inaxaplin, and type 1 diabetes (“T1D”) with VX-880, a stem cell-derived islet cell therapy.

Our research and development approach also includes pursuing multiple modalities tailored to the specific disease area target under investigation, using biomarkers that translate from the bench to the bedside, and advancing multiple candidates into clinical trials with the goal of bringing first-in-class, followed by best-in-class, therapies to patients. In addition to expanding our small molecule programs, we have also advanced an industry-leading portfolio of programs in cell and gene therapies.

Our advancements across multiple disease areas and modalities include:

	Cystic Fibrosis. a lower royalty burden. We continue to pursue next-in-class, small moleculeinvest in serial innovation in our CFTR modulator therapies as well as genetic therapiesprogram and have already discovered the next-generation CFTR modulators, with the goal of creating medicines that deliver even more benefit by bringing more people with CF to carrier levels of sweat chloride, which we believe is the pivotal milestone in the journey toward restoring quality and quantity of life for people living with CF. In addition, we are pursuing a nebulized messenger RNA (“mRNA”) therapy, VX-522, designed for the more than 5,000 people with CF who do not make CFTR protein and, as a result, cannot benefit from our current CF medicines. CFTR modulators. In the past year, we significantly advanced our programSCD and TDT, CASGEVY is now approved for VX-522, a CF mRNA therapeutic designed to treat the underlying cause of CF in these people by enabling cells in the lungs to produce functional CFTR protein. The FDA cleared our investigational new drug (“IND”) application in December 2022 and we have initiated a clinical trial for VX-522 in people with CF; the trial is active and enrolling.
	Sickle Cell Disease and Beta Thalassemia. The Phase 3 studies of exa-cel in patients 12 years of age and older is ongoing,in the United States (“U.S.”), the European Union (“E.U.”), the United Kingdom (“U.K.”), the Kingdom of Saudi Arabia (“Saudi Arabia”), and the Kingdom of Bahrain (“Bahrain”). We estimate approximately 35,000 people with severe SCD and TDT could be eligible for CASGEVY in the U.S. and Europe, with additional eligible people in Saudi Arabia and Bahrain. Pursuant to our global launch strategy, we have been educating physicians, patients, caregivers, payors, and policymakers about the significant disease burden of SCD and TDT and the availability of CASGEVY as is a long-term follow-up study. Two additionalpotentially curative treatment option. We are also actively engaged with treatment centers, policymakers, and payors to ensure that eligible people have broad access to this transformative therapy. Additionally, we continue to study CASGEVY in younger age groups and work on preclinical assets for myeloablative conditioning agents that would have milder side effects, which could broaden the eligible patient population. In our pain program, earlier this year, we announced positive results from our Phase 3 studiesclinical trials evaluating VX-548, a selective, peripherally-acting small molecule inhibitor of the NaV1.8 sodium channel, in pediatricthe treatment of moderate-to-severe acute pain and our plans to submit for regulatory approval in the U.S. by mid-2024. If approved, VX-548 will be the first of a new class of medicines for acute pain in over 20 years. With an estimated 80 million patients continueprescribed medicines for moderate-to-severe acute pain in the U.S. every year, representing over 1 billion calendar days of treatment, we believe acute pain represents a multi-billion dollar market opportunity. We also recently announced positive results from the Phase 2 clinical trial evaluating VX-548 in diabetic peripheral neuropathy (“DPN”), a type of peripheral neuropathic pain (“PNP”), and our intention to enroll.
	Neuropathic Pain. advance VX-548 into pivotal development for DPN. We have initiatedalso began a Phase 2 clinical trial for patients suffering from lumbosacral radiculopathy, another type of PNP. As with acute pain, our goal is to secure a broad PNP indication for VX-548. There are an estimated 10 million patients prescribed medicines for PNP, yet these medicines have significant limitations, including limited efficacy, significant side effects, and carry the risk of addiction. We believe VX-548 holds potential for a superior overall benefit-risk profile in diabetic peripheral neuropathy,PNP and, given the large number of people with these conditions we believe that the U.S. PNP market represents another significant, multi-billion dollar opportunity. In addition to these potential near-term commercial opportunities, we continue to advance our clinical-stage pipeline, which includes programs that have already achieved proof-of-concept, including programs in APOL1-mediated kidney disease (“AMKD”) and type 1 diabetes (“T1D”). In addition, VX-634 and VX-638 are being evaluated in Phase 1 clinical trials in Alpha-1 Antitrypsin Deficiency (“AATD”) and VX-670, a molecule in-licensed from Entrada Therapeutics (“Entrada”), is in Phase 1/2 development for myotonic dystrophy type 1 (“DM1”), an inherited disease affecting approximately 110,000 people in the U.S. and Europe that results in the weakening and destruction of skeletal muscles over time. Recently, we initiated a Phase 1 clinical trial of VX-407, which we are developing for autosomal dominant polycystic kidney disease (“ADPKD”), the most common formgenetic kidney disease, and representing our tenth disease area in the clinic. From a financial perspective, our outstanding performance in 2023 resulted in net product revenues of chronic peripheral neuropathic pain.$9.87 billion with strong operating margins and profitability. We are well-positioned to continue to create long-term value for both patients and shareholders with a portfolio of high-value medicines for CF, SCD and TDT, potential near-term commercial launches for products in acute pain and CF, a broad and deep pipeline across ten disease areas, clinical programs with multiple therapeutic modalities that range from small molecules to genetic and cell therapies, and an excellent financial profile. VERTEX PHARMACEUTICALS INCORPORATED - 2024 Proxy Statement      6 APOL-1 Mediated Kidney Disease. We initiated pivotal development Financial Performance Our CF medicines, TRIKAFTA/KAFTRIO, SYMDEKO/SYMKEVI, ORKAMBI, and KALYDECO, are transforming the lives of inaxaplineligible people around the globe and continue to enrolldrive our financial performance. Our CF net product revenues increased to $9.87 billion in 2023, an increase of 11% or more than $900 million, from our 2022 CF net product revenues. Our total R&D, acquired in-process research and development (“AIPR&D”) and selling, general and administrative (“SG&A”) expenses increased to $4.8 billion compared to $3.6 billion in 2022. This increase was primarily due to higher AIPR&D, increased investment in support of multiple programs that have advanced to mid- and late-stage clinical development, and the costs to support new launches of Vertex’s therapies globally. INCREASING CF NET PRODUCT REVENUES TOTAL R&D, AIPR&D AND SG&A EXPENSES 2023 R&D, AIPR&D AND SG&A EXPENSES VERTEX PHARMACEUTICALS INCORPORATED - 2024 Proxy Statement      7 Marketed Products Our differentiated R&D strategy has delivered not only a decade-long leadership position in CF, but also the Phase 2/3 adaptive clinical trialhistoric, global approvals for CASGEVY, the first CRISPR-based gene-edited cell therapy to be approved in the world, for people with SCD or TDT. In CF, our goal is to bring highly effective treatments to all people with CF, and we began to do just that in January 2012 when KALYDECO was first approved to treat a CF population of approximately 1,000 people in the U.S. Since then, we have focused on growing the number of people eligible for our medicines, expanding access to our medicines in additional geographies, and seeking improved treatment options for all people with CF. Today, our four approved CF medicines are collectively being used to treat nearly three quarters of the approximately 92,000 people with CF in North America, Europe, and Australia. Our CF medicines are used by people in over 60 countries and TRIKAFTA/KAFTRIO is now approved or accessible in more than 40 of these countries. In the near term, we expect our CF business to continue to grow as a result of (i) annualization of patients who recently initiated a CFTR modulator, (ii) label expansions, including into younger age groups and additional eligible mutations globally, (iii) expanded reimbursement, and (iv) the launch of the vanzacaftor triple, which will be a therapeutic option for those who have not yet initiated treatment with AMKD.
	Type 1 Diabetes. We are evaluating VX-880, an investigational stem-cell derived fully-differentiated islet cella CFTR modulator or who have discontinued from a CFTR modulator. In the mid- and longer-term, we foresee growth from (i) increases in the number of people living with CF, (ii) VX-522, a potential new therapy for the treatment of T1D in a Phase 1/2 clinical trial in which patients receive immunosuppressive therapy to protect the islet cellsmore than 5,000 people with CF who cannot benefit from immune rejection. Our Clinical Trial Application (“CTA”) in CanadaCFTR modulators, and our IND(iii) next-generation CFTR modulator regimens. In SCD and TDT, 2023 marked the commercial launch of CASGEVY, following approvals in the U.S., U.K., and Bahrain, and with approvals in the E.U. and Saudi Arabia following closely in early 2024. We estimate approximately 35,000 people with severe SCD or TDT could be eligible for our second programCASGEVY in T1D, VX-264, in which the implanted islet cells are encapsulated in an immunoprotective device, were authorized and we plan to begin screening, enrollment and dosing in both Canada and the U.S. and Europe, with additional eligible people in the coming months. We have also continued pre-clinical development of our hypoimmune program utilizing VX-880 cells,Saudi Arabia and our second hypoimmune program that we are developing in partnership with CRISPRBahrain. Our global launch strategy for CASGEVY is the subject of a Phase 1/2 study that is activefocused on disease education and enrolling patients.
	Alpha-1 Antitrypsin Deficiency (“AATD”). We initiated a first-in-human clinical trialawareness for VX-634, which is the first in a series of next-wave investigational small molecules with significantly improved potencypatients, caregivers, health care professionals, payors, and drug-like properties as compared to our previous alpha-1 antitrypsin (“AAT”) correctors. We also initiated a second Phase 2 clinical trial of VX-864, a first-generation AAT corrector, to assess the impact of longer-term treatment on the liver,policymakers, as well as engagement with the levelsscientific and medical community regarding CASGEVY clinical data. Our strategy is also focused on activating authorized treatment centers to ensure their readiness to treat patients and achieving access for patients through reimbursement agreements with governments and commercial payors, as well as through early access programs where applicable. Since the beginning of functional AAT2023, notable progress includes: The U.S. Food and Drug Administration (“FDA”), the European Commission, the U.K. Medicines and Healthcare products Regulatory Agency (“MHRA”), and Health Canada approved TRIKAFTA/KAFTRIO for the treatment of children with CF 2 to 5 years of age who have at least one F508del mutation in the CFTR gene. The FDA and the European Commission approved the use of ORKAMBI for children with CF from 12 months to less than 24 months of age who are homozygous for the F508del mutation. The FDA approved KALYDECO in children with CF from 1 month to less than 4 months of age. The approval of CASGEVY in the U.S., E.U., U.K., Saudi Arabia, and Bahrain for people 12 years of age and older with SCD or TDT. We have engaged with the Medicaid administrators in all 50 U.S. states, focused on the 25 states with the highest prevalence of SCD patients, and have confirmed pathways to reimbursement in nearly all 25 of these priority states. Approval by the French National Authority for Health of our request for the implementation of an early access program for the use of CASGEVY to treat eligible people with TDT from 12 to 35 years of age. We have begun engagement with payors in the U.K., E.U., Saudi Arabia and Bahrain, including engagement with the National Institute for Health and Care Excellence. Submission for approval of CASGEVY in both SCD and TDT in Switzerland. Activation of 16 authorized treatment centers in the U.S., four authorized treatment centers in Europe, and one in Saudi Arabia. Entry into an agreement with Synergie Medication Collective, a medication contracting organization, covering approximately 100 million people in the U.S., to provide access to CASGEVY. VERTEX PHARMACEUTICALS INCORPORATED - 2024 Proxy Statement      8 Potential Near-Term Launch Opportunities We are preparing for the following potential near-term launches of two new products: Vanzacaftor triple in CF. We continued our strategy of serial innovation by completing three pivotal studies evaluating our once-daily triple combination CFTR modulator therapy, vanzacaftor/tezacaftor/deutivacaftor. Results of the clinical trials demonstrate that this triple combination has the potential to provide additional clinical benefits beyond TRIKAFTA for people with CF who have at least one mutation in their CFTR gene responsive to CFTR modulators. This regimen also has the advantages of once-daily dosing and a lower royalty burden compared with TRIKAFTA. We expect to support the launch of the vanzacaftor triple with our existing commercial infrastructure. We expect to submit global regulatory filings for this triple combination by mid-2024, including in the U.S., the E.U., and Canada for people with CF 6 years and older. In the U.S., we will be using one of our priority review vouchers to shorten the regulatory review period from ten months to six months. VX-548 in acute pain. We completed three Phase 3 clinical trials for VX-548, a non-opioid, investigational selective NaV1.8 inhibitor, for the treatment of moderate-to-severe acute pain. Results of the clinical trials indicate that VX-548 could provide a transformative option for patients suffering from acute pain, based on the suboptimal benefit risk profile of existing agents, including the adverse effects and addictive potential of opioids, and the favorable benefit risk profile of VX-548. For our potential near-term commercial opportunity in acute pain, we are focused on the multi-billion dollar market arising from the estimated 80 million patients in the U.S. who are prescribed a medicine for their moderate-to-severe acute pain each year. More than two-thirds of patients receive acute pain prescriptions either during a hospital or ambulatory surgery center visit or at discharge; these prescriptions are concentrated in approximately 2,000 hospitals and 200 integrated delivery networks, which we believe we can reach with a specialty sales force. We plan to submit a New Drug Application (“NDA”) for the treatment of moderate-to-severe acute pain to the FDA by mid-2024. Research and Development We invest in research and development to discover and develop transformative medicines for people with serious diseases, with a focus on specialty markets. Our research and development strategy combines advances in the plasma.
	Duchenne muscular dystrophy (“DMD”). We are conducting IND-enabling studiesunderstanding of human disease and the science of therapeutics to dramatically advance human health. This strategy was designed to deliver transformative medicines for serious diseases at high rates of speed and success, and it has delivered just that. Our success in moving novel product candidates into clinical trials, successfully completing pivotal development and obtaining marketing approvals offer multiple proof points of this strategy, and include TRIKAFTA/KAFTRIO, SYMDEKO/SYMKEVI, ORKAMBI, and KALYDECO for CF, and CASGEVY for SCD and TDT. The strategy continues to be borne out by our firstpipeline, which includes potential future approvals of the vanzacaftor triple for the treatment of CF and VX-548 for the treatment of acute pain. Our approach to drug discovery has also yielded therapies that have demonstrated clinical proof-of-concept in vivo gene-editing therapy for DMD,additional disease areas, including neuropathic pain with VX-548, AMKD with inaxaplin, and we expectT1D with VX-880, a stem cell-derived islet cell therapy. Our research and development approach also includes pursuing multiple modalities tailored to submit an IND for this program in 2023.
	Myotonic dystrophy type 1 (“DM1”). We are exploringthe specific disease area target under investigation, using biomarkers that translate from the bench to the bedside, and advancing multiple approachescandidates into clinical trials with the goal of bringing first-in-class, followed by best-in-class, therapies to address the underlying causal biology for DM1, and are collaborating with Entrada Therapeutics, Inc. (“Entrada”) on IND-enabling studies for an endosomal escape vehicle therapeutic.
	patients. In addition to theexpanding our small molecule programs, listed above, we have several earlier-stage researchalso advanced an industry-leading portfolio of programs aimed at diseases that fit our R&D strategy.

Our advancements across multiple disease areas and modalities include:

VERTEX PHARMACEUTICALS INCORPORATED - 2023

	Cystic Fibrosis. We continue to pursue next-in-class, small molecule CFTR modulator therapies and have already identified next-in-class correctors and potentiators, as well as genetic therapies for people with CF who do not make full-length CFTR protein and, as a result, cannot benefit from our current CF medicines. For these more than 5,000 people with CF, in collaboration with Moderna, we are developing VX-522, a CF mRNA therapeutic designed to treat the underlying cause of CF in these people by enabling cells in the lungs to produce functional CFTR protein. We have completed dosing in the single ascending dose portion of the clinical trial for VX-522 in people with CF and initiated the multiple ascending dose portion of the trial.
	Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia. We completed enrollment in two global Phase 3 clinical trials evaluating CASGEVY in people 5 to 11 years of age with SCD or TDT, and we are working on preclinical assets for gentler conditioning for CASGEVY, which could significantly broaden the eligible patient population. In addition, we are investigating small molecules for the potential treatment of SCD and TDT.
	Acute Pain. We completed a Phase 1 clinical trial of an oral formulation of VX-993, our next-generation NaV1.8 inhibitor, and plan to initiate a Phase 2 study for the treatment of moderate-to-severe acute pain in 2024. We also anticipate initiating a Phase 1 study of an intravenous formulation of VX-993 in 2024.
	Neuropathic Pain. We announced positive Phase 2 clinical trial results for VX-548 in DPN, a common form of chronic PNP, and will be initiating pivotal clinical development this year. We also initiated a Phase 2 clinical trial of VX-548 in lumbosacral radiculopathy, another type of PNP. In addition, we expect to initiate a Phase 2 clinical trial evaluating an oral formulation of VX-993 for the treatment of PNP in 2024.

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VERTEX PHARMACEUTICALS INCORPORATED - 2023

	APOL-1 Mediated Kidney Disease. We completed enrollment in the Phase 2B dose-ranging portion of the clinical trial evaluating inaxaplin for the treatment of AMKD and have selected the dose for and initiated the Phase 3 portion of the Phase 2/3 pivotal clinical trial.
	Type 1 Diabetes. We completed Parts A and B, and completed enrollment in Part C of the Phase 1/2 clinical trial evaluating VX-880, an allogeneic, stem-cell derived, fully-differentiated, insulin-producing islet cell therapy, used in conjunction with standard immunosuppression, for the treatment of T1D in people with impaired awareness of hypoglycemia and recurrent hypoglycemic events. We have placed the study on a protocol-specified pause, pending review of the totality of the data by the independent data monitoring committee. The clinical trial for our second program in T1D, VX-264, in which the allogeneic stem-cell derived, fully-differentiated, insulin-producing islet cells are encapsulated and implanted in an immunoprotective device to obviate the need for immunosuppression, is a multi-part Phase 1/2 study. We have completed enrollment and dosing in Part A, and Part B of the clinical trial is underway in multiple centers and countries.
	Myotonic dystrophy type 1. We are exploring multiple approaches to address the underlying causal biology for DM1, including an oligonucleotide linked to a circular peptide, VX-670, which was in-licensed from Entrada. The Investigational New Drug Application (“IND”) for the Phase 1/2 clinical trial of VX-670 in people with DM1 has cleared, as have the regulatory submissions in Canada, the U.K. and multiple other geographies. The study has been initiated in Canada and is expected to initiate in other regions in the near term.
	Alpha-1 Antitrypsin Deficiency. We continue to enroll and dose Phase 1 clinical trials evaluating VX-634 and VX-668.
	Autosomal Dominant Polycystic Kidney Disease. We completed pre-clinical enabling studies for VX-407, our first-in-class small molecule corrector that targets the underlying cause of ADPKD in people with a subset of PKD1 genetic variations, in late 2023. The IND for VX-407 in the U.S. has cleared and we have initiated a Phase 1 clinical trial evaluating VX-407 in healthy volunteers in the U.S.
	In addition to the programs listed above, we have several earlier-stage research programs aimed at diseases that fit our R&D strategy, as well as follow-on programs in diseases already in the clinic.

We will continue investing in our research and development programs and fostering scientific innovation by identifying additional product candidates through our internal research efforts and investing in business development transactions to access emerging technologies, products and product candidates.

The following chart represents our clinical stage programs and select pre-clinical programs.

VERTEX PHARMACEUTICALS INCORPORATED - 2024 Proxy Statement     10

VERTEX PHARMACEUTICALS INCORPORATED - 2023

VERTEX PHARMACEUTICALS INCORPORATED - 2024 Proxy Statement     11

Corporate Responsibility

We are a leading global biotechnology company that serially innovates to bring transformative medicines to people with serious diseases. We are committed to operating our business responsibly and disclosing our progress to stakeholders on an annual basis. Our progress and efforts with respect to environmental, social, and governance topics, including community engagement and workplace practices, were recognized broadly in 2023. A selection of awards and recognitions include Fortune 100 Best Employers, JUST Capital’s list of the top 100 Companies Supporting Healthy Families and Communities, Newsweek’s America’s Most Responsible Companies to Work For^® 2023, Forbes’ Best Employers for Diversity, PEOPLE^® Magazine’s 100 Companies That Care, Points of Light’s Civic 50, Science Magazine’s Top Employers, Seramount’s 100 Best Companies, and many others.

 

	Community	Vertex and the Vertex Foundation contributed nearly $35 million in charitable giving in 2022. The Vertex Foundation, a 501(c)(3) nonprofit organization, seeks Our corporate responsibility priorities relate to improvefour objectives fundamental to our business: improving the lives of people with serious diseasesdiseases; fostering a culture of innovation, integrity, and contribute toinclusion; carefully managing our operations and environmental footprint; and making a positive impact in the communities where we are located. Improve the lives of people with serious diseases We are focused on discovering, developing and producing innovative medicines so that people with serious diseases can lead better lives. We invest significantly in research and development, with the majority of operating expenses and our workforce dedicated to that purpose. Once we discover transformative medicines, we then work to ensure patients have access to our medicines. We are deeply committed to understanding the challenges and unmet needs of patients and recognize the importance of partnering with, elevating, and empowering patient communities. Foster a culture of innovation, integrity and inclusion We are focused on fostering a culture of innovation, integrity and inclusion. Our culture of high ethical standards and integrity is one of the key components to our success and all of our directors, officers, employees and contractors are responsible for complying with our Code of Conduct and upholding and demonstrating ethics and integrity in our work every day. We are committed to building an outstanding, committed and passionate team, and we value inclusion, diversity and equity to foster creativity and innovation. Five of our eleven director nominees, including our chief executive officer (“CEO”), are women, and four of our eleven director nominees are from underrepresented communities. As of December 31, 2023, women represented 55% of our global workforce and 40% of our global leadership (vice president and above). In the U.S., in the year ending December 31, 2023, employees from underrepresented ethnic and racial groups represented approximately 41% of our workforce and 45% of new hires. To promote our employees’ continued well-being and development, we also offer a variety of inclusive benefits and career development opportunities. Carefully manage our operations and environmental footprint We are committed to limiting our environmental impact and to operating our business in a sustainable manner. In 2023, we established a new target to reduce our Scope 1 and Scope 2 absolute greenhouse gas (“GHG”) emissions. 49% of our global energy comes from renewable energy sources and we source 100% renewable energy for our U.K.-based international headquarters and R&D facility. For our continued efforts, we received a score of an A- on the 2023 CDP Climate Change survey, demonstrating environmental leadership (global average score is C). We also continually improve standards and incorporate industry best practices with regards to important topics such as employee health and safety as well as our supply chain. Make a positive impact in the communities where we are located We continue to support communities through collaborations, donations, and volunteering across the world. In 2023, Vertex and the Vertex Foundation contributed more than $42 million in charitable giving. The Vertex Foundation, a 501(c)(3) nonprofit organization, seeks to improve the lives of people with serious diseases and contribute to the communities where Vertex is located through education, innovation and health. In 2023, it supported nearly 2,200 nonprofit organizations through the Vertex Foundation Matching Gift program. For our 15th annual Day of Service, a record 60% of employees volunteered in their local communities across 18 countries. VERTEX PHARMACEUTICALS INCORPORATED - 2024 Proxy Statement     12 Director Nominees The following table provides summary information regarding our eleven director nominees. For detailed information about each nominee’s background and areas of expertise, please see Proposal No. 1: Election of Directors.                 Committees Name, Occupation or Experience   Age   Director Since   Independent   AC   MDCC   CGNC   S&T Jeffrey Leiden Executive Chairman, Vertex   68   2009   No                 Reshma Kewalramani CEO and President, Vertex   51   2020   No                 Sangeeta Bhatia John J. and Dorothy Wilson Professor of Health Sciences & Technology/Electrical Engineering & Computer Science, MIT   55   2015   Yes                 Lloyd Carney Former CEO, Brocade Communications   62   2019   Yes                 Alan Garber Interim President and Provost, Harvard University   68   2017   Yes                 Michel Lagarde Executive Vice President and Chief Operating Officer, Thermo Fisher Scientific Inc   50   2023   Yes                 Diana McKenzie Former Chief Information Officer, Workday Former Chief Information Officer, Amgen   59   2020   Yes                 Bruce Sachs Partner Emeritas, Charles River Ventures   64   1998   Yes                 Jennifer Schneider Co-Founder and CEO, Homeward Health, Inc.   49   Nominee   Yes                 Nancy Thornberry Former CEO, Kallyope, Inc.   67   2023   Yes                 Suketu Upadhyay Executive Vice President and Chief Financial Officer, Zimmer Biomet   55   2022   Yes                                                = Chair                             VERTEX PHARMACEUTICALS INCORPORATED- 2024 Proxy Statement     13 2023 Compensation Decisions and Pay-for Performance In 2023, our executive compensation program received substantial support, with approval by approximately 89% of the votes cast at the annual meeting. We believe this support is located through education, innovation and health. In 2022, it supported nearly 2,000 nonprofit organizations through Vertex Volunteersconsistent with our shareholders’ understanding of our business model and the Vertex Foundation Matching Gift programs. In 2022, on our 14th annual Day of Service, 57% of employees volunteered in their local communities around the globe.
	Workplace	long-term value we are creating. Our commitment to inclusion, diversity,management development and equity oncompensation committee (“MDCC”) and our board of directors reviewed our compensation programs and made the following key decisions with respect to 2023 compensation: We maintained the base salary and target equity level for Dr. Reshma Kewalramani, our CEO and President, based on a comparative analysis of companies in our peer group, and maintained her target cash bonus as a percentage of base salary. We maintained target compensation for Mr. Stuart Arbuckle, Dr. David Altshuler, and Mr. Charles Wagner, based on a comparative analysis of companies in our peer group. Dr. Leiden continues to receive no cash compensation for his role as Executive Chairman other than an annual cash payment intended to facilitate participation in the company’s benefit plans, and he will continue to receive equity awards for his fifth year of service as Executive Chairman. Our outstanding performance in 2023 resulted in the board determining that we had achieved a leading rating for 2023 (150 out of a potential 150), with the payment of annual cash bonuses commensurate with this high level of performance. We maintained the mix of equity granted to our NEOs with 50% of the awards consisting of performance stock units (“PSUs”) that vest upon achievement of specific performance goals and 50% consisting of time-vesting restricted stock units (“RSUs”). This mix rewards stock price appreciation and incentivizes long-term tenure. Shareholder Engagement We believe that a robust shareholder outreach program is an important component of maintaining our workforce is long-standingstrong corporate governance practices. We strive for a collaborative approach with shareholders to solicit and deeply ingrained inunderstand a variety of perspectives and interests, and our culture. Threepractice has been to engage with our shareholders regularly over the course of the year. During 2023, we solicited feedback regarding our corporate governance practices from our top 40 shareholders representing approximately 65% of our nine director nominees,outstanding shares. Our integrated outreach team included leaders from our Investor Relations, Human Resources, Corporate Responsibility, Corporate Communications, and Legal teams, and we discussed numerous topics of shareholder interest, including our chiefbusiness strategy, R&D approach, diversity initiatives and metrics, employee engagement and development, corporate governance, political and lobbying disclosures, executive officer (“CEO”), are women,compensation, and four of our nine director nominees are from underrepresented ethnic and racial groups. As of December 31, 2022, women represented 54% of our global workforce and 39% of our global leadership (vice president and above). In the U.S., as of December 31, 2022, employees from underrepresented ethnic and racial groups represented approximately 40% of our workforce and 51% of new hires. We are pleased to have been recognized by numerous best workplace lists, including Seramount’s 100 Best Companies & 100 Best Companies for Dads.environmental sustainability matters. VERTEX PHARMACEUTICALS INCORPORATED - 2024 Proxy Statement     14 Environment Corporate Governance We are committed to limiting our environmental impact and to operating our business in a sustainable manner. In 2022, our Scope 1 and Scope 2 absolute greenhouse gas (“GHG”) emissions were 21.4% below our 2018 baseline. This exceeds our goal to reduce GHG emissions by 20% bymaintaining strong corporate governance practices that promote the end of 2023. We performed well on the CDP Climate Change survey, obtaining a score of B, which demonstrates that we have addressed the environmental impactslong-term interests of our businessshareholders and have ensured good environmentalstrengthen board and management and which was higher than the global average score of C. We continue to source 100% renewable electricity for our U.K. facilities. 83% of the square footage of our buildings globally are, or are expected to be, green certified by the end of 2023. We also have ongoing efforts to minimize waste across all of our sites through employee engagement initiatives, vendor takeback programs and improved product distribution processes.

VERTEX PHARMACEUTICALS INCORPORATED - 2023 Proxy Statement    12

Director Nominees

The following table provides summary information regarding our nine director nominees. For detailed information about each nominee’s background and areas of expertise, please see Proposal No. 1: Election of Directors.

								Committees
Name, Occupation or Experience		Age		Director Since		Independent		AC		MDCC		CGNC*		S&T
Jeffrey Leiden Executive Chairman, Vertex Former CEO and President, Vertex		67		2009		No
Reshma Kewalramani CEO and President, Vertex		50		2020		No
Sangeeta Bhatia John J. and Dorothy Wilson Professor of Health Sciences & Technology/Electrical Engineering & Computer Science, MIT		54		2015		Yes
Lloyd Carney Former CEO, Brocade Communications		61		2019		Yes
Alan Garber Provost, Harvard University		67		2017		Yes
Terrence Kearney Former Chief Operating Officer, Hospira		68		2011		Yes
Diana McKenzie Former Chief Information Officer, Workday Former Chief Information Officer, Amgen		58		2020		Yes
Bruce Sachs General Partner, Charles River Ventures		63		1998		Yes
Suketu Upadhyay Executive Vice President and Chief Financial Officer, Zimmer Biomet		54		2022		Yes

*	Margaret McGlynn currently serves as the Chair of the Corporate Governance and Nominating Committee (“CGNC”). Ms. McGlynn is not standing for re-election at the annual meeting. Following the annual meeting, Lloyd Carney is expected to become the Chair of our CGNC and we expect to make additional changes to the composition of our committees.
=	Chair

VERTEX PHARMACEUTICALS INCORPORATED - 2023 Proxy Statement    13

2022 Compensation Decisions and Pay-for Performance

In 2022, our executive compensation program received substantial support, with approval by approximately 93% of the votes cast at the annual meeting. We believe this support is consistent with our shareholders’ understanding of our business model and the long-term value we are creating. Our management development and compensation committee (“MDCC”) and our board of directors reviewed our compensation programs and made the following key decisions with respect to 2022 compensation:accountability.

 

	We increased the base salary and target equity level for Dr. Reshma Kewalramani, our CEO and President, based on a comparative analysis of companies in our peer group, and maintained her target cash bonus as a percentage of base salary.
	We increased compensation for select named executive officers (“NEOs”), including Dr. David Altshuler and Mr. Charles Wagner, based on a comparative analysis of companies in our peer group.
	We extended Dr. Jeffrey Leiden’s employment agreement by one year, until 2025. Under his amended employment agreement, Dr. Leiden continues to receive no cash compensation for his role as Executive Chairman other than an annual cash payment intended to facilitate participation in the company’s benefit plans, and he will continue to receive equity awards for his fourth and fifth years of service as Executive Chairman.
	Our outstanding performance in 2022 resulted in the board determining that we had achieved a leading rating for 2022 (145 out of a potential 150), with the payment of annual cash bonuses commensurate with this high level of performance.
	The MDCC approved special, one-time equity award grants for Mr. Stuart Arbuckle, our Chief Operating Officer (“COO”). These performance-based and time-based grants are intended to incentivize and retain Mr. Arbuckle, who is in a key commercialization role, during a critical period where we expect to launch multiple transformational therapies in disease areas outside of CF.
	We maintained the mix of equity granted to our NEOs with 50% consisting of performance stock units (“PSUs”) that vest upon achievement of specific performance goals and 50% consisting of time-vesting restricted stock units (“RSUs”). This mix rewards stock price appreciation and incentivizes long-term tenure.

Shareholder Engagement

We believe that a robust shareholder outreach program is an important component of maintaining our strong corporate governance practices. We strive for a collaborative approach with shareholders to solicit and understand a variety of perspectives and interests, and our practice has been to engage with our shareholders regularly over the course of the year.

During 2022, we solicited feedback regarding our corporate governance practices from our top 40 shareholders representing approximately 65% of our outstanding shares. Our integrated outreach team included leaders from our Investor Relations, Human Resources, Corporate Responsibility, and Legal teams, and we discussed numerous topics of shareholder interest, including our business strategy, R&D approach, diversity initiatives and metrics, employee engagement and development, political and lobbying disclosures, executive compensation, and sustainability and climate change matters.

VERTEX PHARMACEUTICALS INCORPORATED - 2023 Proxy Statement    14

VERTEX PHARMACEUTICALS INCORPORATED - 20232024 Proxy Statement     15

Table of Contents

VERTEX PHARMACEUTICALS INCORPORATED - 20232024 Proxy Statement     16

PROXY STATEMENT

This proxy statement is being made available to shareholders of Vertex Pharmaceuticals Incorporated in connection with the solicitation by our board of directors of proxies to be voted at our 20232024 annual meeting of shareholders and at any postponement or adjournment thereof. The annual meeting will be held on Wednesday, May 17, 2023,15, 2024, at 9:00 a.m. (Eastern Time) as a virtual meeting conducted exclusively via live webcast at https://meetnow.global/MSC2Z5F.MQ4XFU9. See Frequently Asked Questions Regarding the Annual Meeting -– How May I Attend the Annual Meeting? below for information regarding attending the virtual annual meeting.

VERTEX PHARMACEUTICALS INCORPORATED - 20232024 Proxy Statement     17

PROPOSAL NO. 1:   ELECTION OF DIRECTORS

Our board of directors has nominated the following current directors - Sangeeta Bhatia, Lloyd Carney, Alan Garber, Terrence Kearney, Reshma Kewalramani, Michel Lagarde, Jeffrey Leiden, Diana McKenzie, Bruce Sachs, Nancy Thornberry, and Suketu Upadhyay - as well as Jennifer Schneider, for election at our 20232024 annual meeting of shareholders to hold office until our 20242025 annual meeting of shareholders. Yuchun Lee and Margaret McGlynn, bothTerrence Kearney, one of our current directors, areis not standing for re-election at our 20232024 annual meeting of shareholders.

Each of the nominees has agreed to be named in this proxy statement and to serve if elected. We believe that all of the nominees will be able and willing to serve if elected. However, if any nominee should become unable or unwilling to serve for any reason, proxies may be voted for another person nominated as a substitute by our board or our board may reduce the number of directors.

Our board of directors is our company’s ultimate decision-making body, except with respect to those matters reserved to the shareholders. Our board selects our senior management team, which in turn is responsible for the day-to-day operations of our company. Our board acts as an advisor and counselor to senior management and oversees its performance.

Board Structure and Composition

The corporate governance and nominating committee (“CGNC”) of our board of directors is responsible for the composition and structure of our board, including identifying, developing, and recommending qualified candidates for board membership. The CGNC regularly reviews director competencies, qualities, skills, and experiences with the goal of ensuring that our board consists of directors who function collegially and effectively and who are able to apply their experience toward meaningful contributions to general corporate strategy and oversight of corporate performance, risk management, organizational development, and succession planning.

Our by-laws provide that the size of our board may range between three and eleven members. We currently have eleven members on our board and expect to have nineeleven members of our board immediately following the 20232024 annual meeting of shareholders. Our CGNC may seek additional director candidates in the future who meet the criteria below to complement the qualifications and experience of our existing board members. Our CGNC may engage a search firm to recommend candidates who satisfy such criteria.

Director Criteria, Qualifications and Experience; Diversity

The CGNC seeks to recommend for nomination experienced directors who have substantive knowledge of our business and industry or who can bring to the board specific and valuable strategic or management capabilities acquired in other industries. The committee expects each of our directors to have proven leadership, sound judgment, the highest ethics and integrity, and a commitment to our success. It also seeks personal qualities that foster a respectful environment in which our directors listen to one another and engage in robust and constructive discussions. These goals for our board composition presuppose a diverse range of viewpoints, experiences, and specific expertise. The CGNC considers a nominee’s personal characteristics and business experience relative to those of our existing board members, including the type of prior management experience, levels of expertise relevant to our business, prior board service, reputation in the business community, personal characteristics such as gender and race, and other factors that the committee believes to be important. When considering whether or not to re-nominate a director for board service, the CGNC also considers whether the director has served as a member of our board for more than 20 years and whether the director is over 72 years of age. Jennifer Schneider was selected and recommended as a nominee for our board of directors by the CGNC based on the criteria outlined above.

Our commitment to diversity and inclusion is demonstrated by the composition of our board nominees, which includes threefive women and four members from underrepresented ethnic and racial groups.

VERTEX PHARMACEUTICALS INCORPORATED - 20232024 Proxy Statement     18

The following table and charts provide information regarding our director nominees:

Leadership Experience. We believe that directors who have held significant leadership positions over extended periods of time provide our company with special insights.
Industry Knowledge. We seek directors with substantive knowledge of the healthcare and biotechnology industries to successfully advise and oversee the strategic development and direction of our company.
Financial Expertise. We believe that an understanding of finance is important for members of our board, and our budgeting processes and financial and strategic transactions require our directors to be financially knowledgeable.
International Perspective. We have significant operations outside the United States and value directors with experience in the operation of complex multinational organizations.
Public Policy and Regulation. We operate in a highly-regulated industry and seek directors who have experience in public policy and the regulation of medicines.
Academic Experience or Technological Background. As a biotechnology company that seeks to develop transformative medicines for patients with serious diseases, we look for directors with backgrounds in academia, science and technology and, in particular, the research and development of pharmaceutical products.
Commitment to Company Values and Goals. We seek directors who are committed to our company and its values and goals and who value the contributions that can be provided by individuals who believe in our company and its prospects for success.
Independence	Y	Y	Y	Y	N	N	Y	Y	Y	Y			N	Y	N	Y
Age	54	61	67	68	50	67	58	63	54	55	62	68	51	50	68	59	64	49	67	55
Tenure on Board	7	4	5	11	3	13	3	24	1	8	5	6	4	0*	14	4	25	0	0**	2
Gender	F	M	M	M	F	M	F	M	M	F	M		F	M		F	M	F		M
Underrepresented Ethnic and Racial Groups

VERTEX PHARMACEUTICALS INCORPORATED - 20232024 Proxy Statement     19

Board Diversity Matrix

Our commitment to diversity and inclusion is also demonstrated by the current composition of our board, which includes four women and fivefour members from underrepresented ethnic and racial groups. The table below provides certain self-identified characteristics of our current directors, in accordance with Nasdaq Rule 5605(f).

Shareholder-Recommended Director Candidates

The CGNC will consider director candidates recommended by shareholders using the same criteria for director selection described above under Director Criteria, Qualifications and Experience; DiversityDiversity. . Shareholders recommending candidates for consideration should submit any pertinent information regarding the candidate, including biographical information and a statement by the proposed candidate that the candidate is willing to serve if nominated and elected, by mail to our corporate secretary at our offices at 50 Northern Avenue, Boston, Massachusetts 02210. If a shareholder wishes to nominate a candidate to be considered for election as a director at the 20242025 annual meeting of shareholders using the procedures set forth in our by-laws, the shareholder must follow the procedures described in our by-laws and summarized in the section titled Other Information—Shareholder Proposals and Nominations for Director for the 20242025 Annual Meeting on page 8491 of this proxy statement. If a shareholder wishes to solicit proxies for a shareholder nominee for election to our board at the 2024 annual meeting of shareholders pursuant to Rule 14a-19 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), the shareholder must follow the procedures set forth in Rule 14a-19 of the Exchange Act and our by-laws.

Our by-laws provide for proxy access, a process that allows qualifying shareholders to nominate a director candidate for consideration at an annual meeting of shareholders and have such candidate be included in our proxy materials for the applicable shareholder meeting. The key elements of our proxy access by-law are as follows:

The above table is only a summary of our proxy access by-law and is qualified in its entirety by our by-laws. A shareholder who wishes to nominate a proxy access nominee to be considered for election as a director at the 20242025 annual meeting of shareholders must follow the procedures set forth in our by-laws as well as those described in Other Information—Shareholder Proposals and Nominations for Director for the 20242025 Annual Meeting on page 8491 of this proxy statement.

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Majority Votes Cast Standard

Our by-laws provide for a majority votes cast standard for uncontested elections of our directors. Under our by-laws, director nominees in an uncontested election who receive more votes cast “for” such director nominee than “against” such director nominee are elected. Our board’s policy is that any nominee for director in an uncontested election who receives a greater number of votes “against” than votes “for” the nominee’s election shall promptly tender their resignation to the chair of our board following certification of the shareholder vote. The CGNC will promptly consider the tendered resignation. Based on all factors it deems in its discretion to be relevant, the CGNC will recommend that our board either accept or reject the resignation and may recommend that the board adopt measures designed to address any issues perceived to underlie the election results. Our board will then act on the CGNC’s recommendation. We will promptly disclose our board’s decision, including, if applicable, the reasons for rejecting the tendered resignation. Any director whose resignation is being considered under this policy will not participate in the CGNC or board considerations, recommendations or actions with respect to the tendered resignation.

Director Nominees

Other Public Company BoardsBoards::      None		Sangeeta Bhatia
		Age:54 55   Director Since: 2015	Board Committees:      Chair – Science and Technology Committee    Member – Corporate Governance and Nominating Committee
		Experience:    Professor at the Massachusetts Institute of Technology (“MIT”); John J. and Dorothy Wilson Professor of Health Sciences & Technology/Electrical Engineering & Computer Science, since 2005    Co-founderCo-Founder of Ropirio Therapeutics, a private biotechnology company focused on lymphatic medicine since 2023 Co-Founder of Amplifyer Bio, a private biotechnology company focused on oncology diagnostics, since 2023 Co-Founder of Matrisome Bio, a private biotechnology company, since 2023 Co-Founder of Port Therapeutics, a private company focused on thermal bioswitches in oncology, since 2022    Co-founderCo-Founder of Satellite Bio, a private company focused on developing satellite organs as living therapeutic solutions, since 2020    Co-founderCo-Founder of Glympse Bio, a private company focused on developing in vivo sensing technology dedicated to disease monitoring, sincefrom 2018 until it was acquired by Sunbird Bio, Inc. in August 2023    Professor of bioengineering and medicine at the University of California at San Diego, from 1998 through 2005    Investigator for the Howard Hughes Medical Institute, a member of the Department of Medicine at Brigham and Women’s Hospital, a member of the Broad Institute and a member of the Koch Institute for Integrative Cancer Research    Holds a Sc.B. in biomedical engineering from Brown University, an S.M. and Ph.D. in Mechanical Engineering from MIT, and an M.D. from Harvard Medical School
		Key Skills and Qualifications: Dr. Bhatia is a leading academic scientist and medical researcher. Her extensive experience in the field of biomedical engineering and in-depth understanding on the use of advanced technologies in medical research provide valuable insights to our board of directors, including with respect to our key research and development initiatives.

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Other Public Company BoardsBoards::      Visa Inc.    Grid Dynamics Holdings Inc.		Lloyd Carney
		Age:61 62   Director Since: 2019	Board Committees:      MemberChair – AuditCorporate Governance and FinanceNominating Committee    Member – Management Development and Compensation Committee
		Experience:      Chief Acquisition Officer of Carney Technology Acquisition Corp. II, a special purpose acquisition corporation, from October 2020 until February 2023    Chief Executive Officer of ChaSerg Technology Acquisition Corp., a technology acquisition company, from September 2018 until March 2020    Chief Executive Officer and Director of Brocade Communications Systems Inc., a global supplier of networking hardware and software, from 2013 until it was acquired by Broadcom in 2017    Chief Executive Officer of Xsigo Systems, a cloud-based infrastructure solutions provider, until it was acquired by Oracle in 2012    Chief Executive Officer and Chairman of Micromuse Inc., a software solutions provider for business and service assurance, from 2003 until it was acquired by IBM in 2006    Previously held senior leadership roles at Juniper Networks, Inc., Nortel Networks Inc., and Bay Networks, Inc.    Member of the Boardboard of Directorsdirectors of Nuance Communications Inc., a publicly traded AI-enabled communication company, until it was acquired by Microsoft Corp in March 2022    Ambassador/Special Investment Envoy for Technology Jamaica, since May 2023 Chancellor, University of Technology, Jamaica, a public university in Jamaica, since August 2022 Holds a Bachelor of Science degree in Electrical Engineering Technology from Wentworth Institute of Technology, a Master of Science degree in Applied Business Management from Lesley College, and ana Honorary Doctorate degree in Engineering from Wentworth Institute of Technology and a Honorary Doctorate degree in Technology from University of Technology Jamaica
		Key Skills and Qualifications:   Mr. Carney brings strong business judgment, honed through his time as a senior executive and board member of multiple global technology companies, to our board of directors. Mr. Carney has extensive corporate leadership experience, including service as the chief executive officer of several technology companies, as well as financial expertise.

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Other Public Company BoardsBoards::      Exelixis, Inc.		Alan Garber
		Age:67 68   Director Since: 2017	Board Committees:    Member – Audit and Finance Committee    Member – Science and Technology Committee
		Experience:      Interim President of Harvard University since January 2024; Provost of Harvard University and the Mallinckrodt Professor of Health Care Policy at Harvard Medical School, a Professor of Economics in the Faculty of Arts and Sciences, Professor of Public Policy in the Harvard Kennedy School of Government, and Professor in the Department of Health Policy and Management in the Harvard T.H. Chan School of Public Health, since 2011    Henry J. Kaiser Jr. Professor, a Professor of Medicine, and a Professor (by courtesy) of Economics, Health Research and Policy, and of Economics in the Graduate School of Business at Stanford University, from 1998 until 2011    Member of the National Academy of Medicine, the American Society of Clinical Investigation, the Association of American Physicians, and the American Academy of Arts and Sciences    Fellow of the American Association for the Advancement of Science, the American College of Physicians, and the Royal College of Physicians    FormerCurrent Research Associate with the National Bureau of Economic Research and served for nineteen years as founding Director of its Health Care Program    Previously served as a member of the National Advisory Council on Aging at the National Institutes of Health, as a member of the Board of Health Advisers of the Congressional Budget Office, and as Chair of the Medicare Evidence Development and Coverage Advisory Committee at the Centers for Medicare and Medicaid Services    Holds an A.B. summa cum laude, an A.M. and a Ph.D., all in Economics, from Harvard University, and an M.D. with research honors from Stanford University
		Key Skills and Qualifications:   Dr. Garber brings extensive leadership experience and knowledge regarding science, medicine, and the healthcare industry and in particular healthcare economics to our board of directors. His expertise in health care policy and as an advisor to government agencies provides our board important insights and perspectives on the issues facing our company.

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Other Public Company Boards:    None		Terrence Kearney
		Age: 68 Director Since: 2011	Board Committees:    Chair – Audit and Finance Committee    Member – Management Development and Compensation Committee
		Experience:Company Boards:      Chief Operating Officer of Hospira, Inc., a specialty pharmaceutical and medication delivery company, from 2006 until 2011    Senior Vice President, Finance, and Chief Financial Officer of Hospira from 2004 to 2006    Vice President and Treasurer of Abbott Laboratories, from 2001 to 2004    Divisional Vice President and Controller for Abbott’s International Division, from 1996 until 2001    Member of the following Boards of Directors of Levo Therapeutics, Inc., a biotechnology company focused on developing treatments for Prader-Willi Syndrome, from 2018 to June 2022; Acceleron Pharma Inc., a publicly traded biopharmaceutical company, from 2014 until it was acquired by Merck in November 2021; Innoviva (formerly known as Theravance, Inc.), a publicly traded royalty management company, from 2014 through 2016; and AveXis, Inc., a publicly traded gene therapy company, from 2016 until it was acquired by Novartis in 2018    Holds a B.S. in biology from the University of Illinois and an M.B.A. from the University of Denver Key Skills and Qualifications: Mr. Kearney’s corporate leadership experience, industry knowledge and financial expertise make him a valuable contributor to our board of directors. He has a practical perspective on the management of global pharmaceutical operations, including commercial, manufacturing and research and development activities, and financial management strategies. Mr. Kearney is an “audit committee financial expert,” as defined by the Securities and Exchange Commission (“SEC”), with particular experience in pharmaceuticals.

Other Public Company Boards:    Ginkgo Bioworks Holdings, Inc.		Reshma Kewalramani
		Age:50 51   Director Since: 2020	Position:    Chief Executive Officer and President
	Experience:      Chief Executive Officer and President of Vertex Pharmaceuticals Incorporated since April 2020    Executive Vice President and Chief Medical Officer of Vertex from 2018 through March 2020    Senior Vice President, Late Development of Vertex from 2017 until 2018    Served in roles of increasing responsibility at Amgen Inc. from 2004 to 2017, most recently as Vice President and Head of U.S. Medical Organization    Industry representative to the FDA’s Endocrine and Metabolic Drug Advisory Committee from 2014 through 2019    Holds a B.A. from Boston University and an M.D. from Boston University School of Medicine; Dr. Kewalramani completed her internship and residency in Internal Medicine at the Massachusetts General Hospital and her fellowship in nephrologyNephrology at the Massachusetts General Hospital and Brigham and Women’s Hospital combined program    Dr. Kewalramani also completed the General Management Program at Harvard Business School and is an alumna of the school
		Key Skills and Qualifications:   Dr. Kewalramani possesses strong leadership qualities, industrysignificant experience overseeing and research, development and commercializationscaling the operations of a global enterprise, deep expertise in drug development, and wide-ranging experience in policy matters, demonstrated through her services as a senior executive in the biotechnology sector. She is a physician-executive with extensive industry knowledge garnered through her scientific and medical roles and experience as a global senior leader across multiple disease areas and all stages of drug development. She provides our board of directors with in-depth knowledge of our company gained during her various senior management roles within Vertex and through the day-to-day leadership of our executives as CEO.

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Other Public Company BoardsBoards::      None		NoneMichel Lagarde
		Age: 50   Director Since: 2023	Board Committees: Member – Audit and Finance Committee
		Experience: Executive Vice President and Chief Operating Officer at Thermo Fisher Scientific Inc. (“Thermo Fisher”), a supplier of analytical instruments, life sciences solutions, specialty diagnostics, laboratory, pharmaceutical and biotechnology services, since January 2022; Thermo Fisher is a supplier to Vertex Executive Vice President at Thermo Fisher from 2019 through 2021 Senior Vice President and President, Pharma Services at Thermo Fisher from 2017 to 2019, joining Thermo Fisher as Senior Vice President, as a result of its acquisition of Patheon N.V., a pharma services company, in 2017 President and Chief Operating Officer of Patheon N.V. from 2016 to 2017 Managing Director of JLL Partners, a private equity firm focused on healthcare, from 2008 to 2016 Holds a bachelor’s degree in business administration from European University in Antwerp and an executive master’s degree in finance and control from the University of Maastricht and University of Amsterdam
		Key Skills and Qualifications: Mr. Lagarde has deep experience across numerous segments of the health care industry and markets around the world, as well as a successful track record of growing and scaling profitable businesses. He brings to our board of directors strong leadership experience in biotechnology and pharmaceutical development and commercial manufacturing services as well as financial expertise across several international markets.

Other Public Company Boards: None		Jeffrey Leiden
		Age:67 68   Director Since: 2009	Position:      Executive Chairman
		Experience:      Chief Executive Officer and President of Vertex Pharmaceuticals Incorporated from 2012 through March 2020    Chairman of Board of Directors of Vertex since 2012; previously served as lead independent director from 2010 through 2011    Managing Director at Clarus Ventures, a life sciences venture capital firm, from 2006 to 2012    President and Chief Operating Officer of Abbott Laboratories, Pharmaceuticals Products Group and a member of the Boardboard of Directorsdirectors of Abbott Laboratories from 2001 to 2006    Held several academic appointments from 1987 to 2000, including the Rawson Professor of Medicine and Pathology and Chief of Cardiology and Director of the Cardiovascular Research Institute at the University of Chicago, the Elkan R. Blout Professor of Biological Sciences at the Harvard School of Public Health, and Professor of Medicine at Harvard Medical School    Elected member of both the American Academy of Arts and Sciences and the Institute of Medicine of the National Academy of Sciences    Member of the Boardboard of Directors of Massachusetts Mutual Life Insurance Company, an insurance company    Member of the Board of Directorsdirectors of Quest Diagnostics Incorporated, a publicly traded medical diagnostics company, from 2014 to May 2019; member of the Boardboard of Directorsdirectors and non-executive Vice Chairman of Shire plc, a specialty biopharmaceutical company, from 2006 to 2012; Chairman of Revolution Healthcare Acquisition Corp., a special purpose acquisition corporation, from April 2021 to December 2022 Dr. Leiden received his M.D., Ph.D. and B.A. degrees from the University of Chicago
		Key Skills and Qualifications:   Dr. Leiden possesses strong leadership qualities, demonstrated through his service as a senior executive in the biotechnology and pharmaceutical industries and as a life sciences venture capitalist, and has extensive knowledge of the science underlying drug discovery and development through his experiences as a distinguished physician, scientist, and teacher. As our former CEO and as a former senior executive at Abbott Laboratories, he brings a global perspective to our business and public policy issues facing our company. He also provides our board of directors with in-depth knowledge of our company and our corporate strategy.

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Other Public Company BoardsBoards::      MetLife Inc.    agilon health, inc.		Diana McKenzie
		Age:58 59   Director Since: 2020	Board Committees:    Member – Corporate Governance and Nominating Committee    Member – Science and Technology Committee Member – Management Development and Compensation Committee
		Experience:      Chief Information Officer of Workday, Inc., a cloud-based financial and human capital management software company, from 2016 until April 2019    Held roles of increasing responsibility at Amgen Inc., a biotechnology company, for 12 years, most recently serving as Senior Vice President and Chief Information Officer    Held various leadership roles at Eli Lilly and Company, a pharmaceutical company, for 17 years, focused on drug development, reducing time to market and improving technology and security standards    Member of the Boardboard of Directors of Paradox AI; Special Advisor to Brighton Park Capital    Member of the Board of Directorsdirectors of Change Healthcare, Inc., a publicly traded healthcare technology company, from August 2019 until it was acquired by United Health Group in October 2022    Holds a Bachelor of Science degree in Computer Information Systems from Purdue University and completed the Information Technology Management Program at University of California, Los Angeles and the CERT Certification for Cybersecurity Oversight from Carnegie Mellon’s Software Engineering Institute
		Key Skills and Qualifications:   Ms. McKenzie has corporate leadership experience and industry knowledge that make her a valuable contributor to our board of directors. Her service as an executive and innovator in the biotechnology and technology industries and as a member of the board of directors of public companies involved in healthcare issues provide her with multiple perspectives on our industry. Ms. McKenzie brings extensive experience growing, scaling, and transforming global businesses in the healthcare and software industries.

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Other Public Company BoardsBoards::      None		Bruce Sachs
		Age:63 64   Director Since: 1998	Board Committees:      Chair – Management Development and Compensation Committee    Member – Corporate Governance and Nominating Committee
		Experience:      General Partner Emeritus at Charles River Ventures (“CRV”), a venture capital firm, since 1999firm; General Partner at CRV for more than 20 years, including more than 10 years as the Managing Partner    Executive Vice President and General Manager of Ascend Communications, Inc. from 1998 to 1999    President and Chief Executive Officer of Stratus Computer, Inc. from 1997 tountil it was acquired by Ascend Communications in 1998    Executive Vice President and General Manager of the Internet Telecom Business Group at Bay Networks, Inc. from 1995 to 1997    President and Chief Executive Officer of Xylogics, Inc. from 1993 tountil it was acquired by Bay Networks in 1995    Holds a B.S.E.E. in electrical engineering from Bucknell University, an M.E.E. in electrical engineering from Cornell University, and an M.B.A. from Northeastern University
		Key Skills and Qualifications:   Mr. Sachs brings strong business judgment, honed through his experience developing business strategy as a senior executive and in venture capital, to our board of directors. Mr. Sachs has a deep understanding of our business and the global business environment along with expertise in the technology that supports our infrastructure and operations. In addition, Mr. Sachs has extensive business leadership experience, including service as a technology company CEO, as well as financial expertise.

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Other Public Company BoardsBoards::      None		Suketu “Suky” UpadhyayJennifer Schneider
		Age:54 49   Director Since: Nominee2022	Board Committees:    Member – Audit and Finance Committee
		Experience:   Co-Founder and CEO of Homeward Health, Inc., a company committed to rearchitecting the delivery of health and care in rural America in partnership with communities, since 2022 President of Livongo Health, a biotechnology company, from December 2018 to October 2020, and served as the Chief Medical Officer from September 2015 to December 2018 Served in multiple leadership roles at Castlight Health, Inc., a healthcare navigation company, from 2010 to 2015, most recently as Chief Medical Officer Member of the board of directors at Revolution Healthcare Acquisition Corp., a special purpose acquisition company, from March 2021 to December 2022 Member of the board of directors at Health Assurance Acquisition Corp., a special purpose acquisition company, from September 2020 until it liquidated in November 2022 Holds a B.S. in Biology from the College of the Holy Cross, an M.D. from Johns Hopkins School of Medicine, and an M.S. in Health Services Research from Stanford University
		Key Skills and Qualifications: Dr. Schneider has deep knowledge and expertise in healthcare and technology. She has led or held senior leadership roles in multiple companies focused on delivering innovative solutions in healthcare management. At Livongo, Dr. Schneider led the company through the largest consumer digital health initial public offering in history as well as its merger with Teladoc Health, the industry’s largest ever merger. Dr. Schneider brings extensive experience as a practicing physician and as a leader building healthcare companies that use technology to provide access to clinical services.

Other Public Company Boards: Denali Therapeutics Schrödinger Inc.		Nancy Thornberry
		Age: 67 Director Since: 2023	Board Committees: Member – Science and Technology Committee
		Experience: Founder and Chief Executive Officer of Kallyope, Inc. (“Kallyope”), a private biotechnology company, from November 2015 to October 2021, and served as Chair of Research and Development through December 2023 Self-employed as a consultant to companies in the biotechnology and pharmaceutical industries from August 2013 to October 2015 Served in roles on increasing responsibility at Merck & Co., Inc., a pharmaceutical company, for more than 30 years, most recently as Senior Vice President and Franchise Head, Diabetes and Endocrinology Holds a B.S. in Chemistry and Biology from Muhlenberg College
		Key Skills and Qualifications: Ms. Thornberry has over 30 years of experience in the pharmaceutical and biotechnology industries and her scientific leadership has spanned across drug discovery, research & development, as well as business development. She brings to our board of directors leadership experience in critical scientific roles driving innovation at both public and private companies. Her industry experience, scientific acumen and strategic thinking brings great value to our board of directors.

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Other Public Company Boards: None		Suketu Upadhyay
		Age: 55 Director Since: 2022	Board Committees: Chair – Audit and Finance Committee
		Experience: Executive Vice President and Chief Financial Officer of Zimmer Biomet, a leading global innovator and manufacturer of orthopedic solutions, since July 2019    Senior Vice President, Global Financial Operations at Bristol-Myers Squibb from 2016 to June 2019    Executive Vice President and Chief Financial Officer of Endo International from 2013 to 2016    Previously served as interim Chief Financial Officer and Senior Vice President of Finance, Corporate Controller and Principal Accounting Officer of Becton Dickinson and Senior Vice President of Global Financial Planning and Analysis and Vice President and Chief Financial Officer of Becton Dickinson’s international business    Previously held a number of global finance and strategy roles across AstraZeneca and Johnson & Johnson, including Research and Development, Supply Chain, Commercial Operations and Business Development    Spent the early part of his career in public accounting with KPMG, earning his CPA designation and his CMA designation (each designation currently inactive)    Holds a Bachelor of Science in Finance from Albright College and an MBA from The Fuqua School of Business at Duke University
		Key Skills and Qualifications:   Mr. Upadhyay has extensive experience in the health care industry in financial roles covering all major areas of a fully integrated life sciences business. His service as an executive in the pharmaceutical, hospital supply, and medical device industries provide him with multiple perspectives on our industry. His knowledge and expertise make him a valuable contributor to our board of directors and management.

Board Recommendation

In each of the director nominee biographies, we highlight the specific experience, qualifications, attributes, and skills that led the board of directors to conclude that the director nominee should serve on our board at this time.

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CORPORATE GOVERNANCE AND RISK MANAGEMENT

We are committed to good corporate governance and integrity in our business dealings. Our governance practices are documented in our Statement of Corporate Governance Principles, which addresses the role and composition of our board of directors and the functioning of the board and its committees. You can find our governance documents, including our Statement of Corporate Governance Principles, charters for each committee of the board, and our Code of Conduct, on our website www.vrtx.com under “Investors—Corporate Governance—Governance Documents.”

Director Independence

Our board of directors has determined that nine of our eleven current directors and seven of our nine director nominees qualify as “independent” under the definition of that term adopted by The Nasdaq Stock Market LLC (“Nasdaq”). In addition, Mr. Kearney, one of our current directors who is not standing for re-election at our 2024 annual meeting of shareholders, was determined to be an independent director. Our independent director nominees are Dr. Bhatia, Mr. Carney, Dr. Garber, Mr. Kearney,Lagarde, Ms. McKenzie, Mr. Sachs, Dr. Schneider, Ms. Thornberry, and Mr. Upadhyay. Our independent directors meet in executive session without management at each regularly scheduled board meeting. Each of the board committees is composed of independent directors.

Board Leadership Structure

Our board recognizes that one of its key responsibilities is to periodically evaluate the optimal leadership structure to ensure robust independent oversight of management and an engaged and effective board with complementary qualities, perspectives, and experiences. Given the dynamic and competitive environment in which we operate, the board believes that its optimal leadership structure may vary as circumstances warrant. The board values the flexibility to determine its optimal model for board leadership at any given time. As such, the board annually reviews its leadership structure and may choose a different leadership structure if circumstances should arise that lead it to believe that such structure would promote the long-term interests of our shareholders.

Our governing documents permit the roles of Chair of the board and CEO to be filled by the same or different individuals. To ensure robust independent leadership on the board, our corporate governance guidelines also require our independent directors to elect a Lead Independent Director if the Chair of the board is a member of management or does not otherwise qualify as independent under the company’s director independence standards.

Currently, the board believes it is in the best interests of the company and our shareholders for the roles of Chair of the board and CEO to be separated, supported by a Lead Independent Director who has oversight responsibilities. Separating these positions at this time allows our CEO to focus on strategic decisions and our day-to-day business operations and performance, allows the Chair, our former CEO, to drive organization and effectiveness of the board in addition to his specifically delineated executive responsibilities, and allows our Lead Independent Director to lead the board in its fundamental role of providing advice to and independent oversight of management, including promoting communication between management and our board and supporting our board’s oversight of risk and other key governance matters. The board believes that this structure provides our board with independent leadership, while providing the benefit of having our former CEO chair regular board meetings and our current CEO participate in regular board meetings as a director.

The board annually evaluates whether combining or separating the roles of Chair of the board and CEO is in the best interests of the company and our shareholders. In its evaluation, the board considers a number of factors, including: (1) the individuals currently in the roles of CEO, Chair and Lead Independent Director and their record of leadership and performance in their roles; (2) current composition of the board; (3) the effectiveness of the policies, practices, and people in place to help ensure strong, independent board oversight; (4) the company’s performance and the effect the leadership structure could have on its performance; (5) the board’s performance and the effect the leadership structure could have on the board’s performance; (6) the Chair and Lead Independent Director’s performance in their respective roles; and (7) the views of our shareholders. A change in any of these factors could lead the board to determine in the future that it is more appropriate to have a different board leadership structure. Any such changes to our board leadership structure would be communicated to our shareholders through our annual proxy statement and as otherwise required by law.

Executive Chair of the Board

Since 2020, Dr. Leiden has served as our Executive Chairman. In this role, Dr. Leiden not only serves as the Chair of our board, but also continues to have executive responsibilities as described below, with our corporate business development function, our cell and genetic therapy programs, and our external communications and government affairs activities.activities, as described below. The board believes this leadership structure is currently in the best

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interest of shareholders because Dr. Leiden, as a long-time executive of the company, has a vast knowledge and deep understanding of the company and its strategic plans, people, and operations. This company-specific experience, along with Dr. Leiden’s extensive knowledge

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of the industry and comparable organizations and broad involvement in drug discovery and development, as well as his distinguished tenure as Chair of the board since 2012 and wide-ranging experience in corporate governance and leadership, provide him with outstanding advising and oversight capabilities as Chair of the board. Dr. Leiden’s specific responsibilities include:

	overseeing the corporate business development function;
	providing guidance on our cell and genetic therapy programs;
	supporting external communications, including with our shareholders;
	assisting the CEO with specific government affairs activities;
	collaborating with CGNC, the Lead Independent Director, and the CEO on the identification, evaluation, and recruitment of potential candidates for board membership and consideration of overall board composition;
	collaborating with CGNC and the Lead Independent Director on the recommendation to the board of individual directors to serve as members and chairs of each board committee;
	collaborating with CGNC and the Lead Independent Director on development and recommendation to the board of the annual self-evaluation process for the board and its committees; and
	collaborating with CGNC and the lead independent director on the oversight of the CEO succession planning process, including assistance in recruiting and identifying potential candidates for the CEO position.

Lead Independent Director

Our board believes that strong, independent board leadership is a critical aspect of effective corporate governance. Our corporate governance guidelines require that if the Chair is not an independent director, the independent directors shall elect a Lead Independent Director. Since December 2011, Mr. Sachs has served as our Lead Independent Director or Co-Lead Independent Director. Mr. Sachs’ extensive business leadership experience as a CEO, a venture capitalist, and a director of the company, combined with his financial expertise, strongly positions him to provide independent leadership of the board and its responsibility for identifying and assessing company risks and providing guidance on risk mitigation strategies.

The board recognizes the importance of appointing a strong Lead Independent Director to maintain a counterbalancing structure to ensure that the board functions in an appropriately independent manner and to hold management accountable for our continued success. As such, the responsibilities of the Lead Independent Director are designed to ensure that our independent directors are empowered to provide robust guidance to, and oversight of, management. Our Lead Independent Director’s responsibilities include:

	calling and leading regular and special meetings of the independent directors;
	serving as a liaison between our management and independent directors;
	facilitating discussion and open dialogue among the independent directors, including with respect to the consideration of company risks and risk mitigation strategies;
	presiding at executive sessions of the independent directors;
	reviewing the planned dates for regularly scheduled board meetings and the primary agenda items for each meeting, which allows the Lead Independent Director to provide input and direction with respect to the matters that come before the board, including risk matters;
	providing board leadership if the Chair of the board or CEO may be (or may be perceived to be) in conflict with the best interests of the company and its shareholders;
	representing the board in certain communications with shareholders when requested and as appropriate;
	collaborating with CGNC, the Chair of the board, and the CEO on the identification, evaluation, and recruitment of potential candidates for board membership and consideration of overall board composition;
	collaborating with CGNC and the Chair of the board on the recommendation to the board of individual directors to serve as members and chairs of each board committee;
	collaborating with CGNC and the Chair of the board on development and recommendation to the board of an annual self-evaluation process for the board and its committees; and
	collaborating with CGNC and the Chair of the board on the oversight of the CEO succession planning process, including assistance in recruiting and identifying potential candidates for the CEO position.

We believe our board structure provides consistent and strong independent oversight of management, while also facilitating a collaborative and collegial environment for board deliberations and decision-making.

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Board Committees

Our board of directors has established various committees, each of which has a written charter, to assist in discharging its duties: the audit and finance committee (“audit committee”), the CGNC, the MDCC, and the science and technology committee (“S&T committee”). Each member of the audit committee, CGNC, MDCC and S&T committee is an independent director as that term is defined by the applicable SEC and Nasdaq rules. The primary responsibilities of each of the committees are set forth below, and the committee memberships are provided in the table appearing on page 3032 of this proxy statement.

Each of the committees has the authority, as its members deem appropriate, to engage outside legal counsel or other experts or consultants to assist the committee in carrying out its responsibilities. Each board committee has the authority to delegate any of its responsibilities to one or more subcommittees comprised of at least one member of the committee to the extent deemed appropriate but subject always to the general oversight of the board.

Audit and Finance Committee

The primary purposes of the audit committee are to:

	assist our board’s oversight of our accounting and financial reporting processes, including financial controls and audits of our financial statements;
	appoint, oversee, and replace, if necessary, our independent registered public accounting firm engaged for the purpose of preparing or issuing an audit report or performing other audit, review, or attestation services;
	review and discuss our annual audit, quarterly reviews and related disclosures, and oversee our internal audit function;
	review and make recommendations to our board concerning our financial structure, financial strategy, and risks;
	oversee our policies and programs and address risks related to our programs, our financial and accounting systems, accounting policies and investment strategies, internal audit function, and cybersecurity, and review material tax matters, including tax structure and strategies;
	address risks arising from related person transactions; and
	assist our board’s oversight of our Code of Conduct, related policies and procedures, and ongoing compliance matters as needed.

Our independent registered public accounting firm reports directly to, and is held accountable by, our audit committee in connection with the audit of our annual financial statements and related services.

Mr. Kearney,Upadhyay the chair of our audit committee, is our “audit committee financial expert” as that term is defined in applicable rules and regulations of the SEC, and is independent according to the applicable listing standards of Nasdaq. In addition, other members of the audit committee are qualified to serve as an audit committee financial expert under the SEC rules and regulations. The report of the audit committee appears on page 3943 of this proxy statement.

Our audit committee reviews and approves all transactions with related persons that are required to be disclosed by us pursuant to Item 404(a) of Regulation S-K promulgated by the SEC, except for transactions, if any, related to the employment of executive officers, which would be recommended for board approval by the MDCC. Our policies and procedures with respect to transactions with related persons are governed by our written Related Party Transaction Policy. Pursuant to this policy, related party transactions include transactions, arrangements or relationships in which our company is a participant, the amount involved exceeds $120,000, and one of our executive officers, directors, director nominees or 5% shareholders or their immediate family members, whom we refer to as related persons, has a direct or indirect material interest, except where disclosure of such transaction would not be required pursuant to Item 404(a) of Regulation S-K. As appropriate for the circumstances, our audit committee reviews and considers the related person’s interest in the related party transaction and such other factors as it deems appropriate. In 2022,2023, we had no transactions considered to be a related party transaction pursuant to Item 404(a) of Regulation S-K.

Corporate Governance and Nominating Committee

The primary purposes of the CGNC are to:

	assist our board of directors in developing and implementing our corporate governance principles;
	recommend the size, composition, and leadership structure of our board and its committees;
	identify and recommend to our board qualified individuals for board membership, accounting for the appropriate balance of knowledge, experience, skills, expertise, tenure, and diversity;

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oversee the CEO succession planning process and assist the board in recruiting and evaluating potential candidates;

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	develop and recommend to our board an annual self-evaluation process to assess the effectiveness of our board and its committees, and coordinate this process;
	oversee risks related to the company’s governance structure; and
	review and make recommendations with respect to our committee charters.

Management Development and Compensation Committee

The primary purposes of the MDCC are to:

	assess the overall compensation programs of the company and adopt a written statement of compensation philosophy and objectives;
	oversee and make recommendations to the board regarding compensation and development of our executives;
	recommend to the board (i) ratings for the company performance against company goals for the prior year and (ii) goals and weighting of goals for the next year;
	oversee risks associated with our compensation policies, management resources and structure, and management development and selection processes;
	oversee and make recommendations to the board regarding the compensation of our non-employee directors; and
	review and approve our benefit and equity plans.plans; and
	oversee and make recommendations to the board regarding the adoption, amendment, administration, and termination of any recoupment policy of the company.

See Compensation Discussion and Analysis—Detailed Discussion and Analysis below for a discussion of the MDCC’s role in overseeing executive compensation.

The report of the MDCC appears on page 6673 of this proxy statement.

Science and Technology Committee

Our S&T committee assists our board of directors in its responsibilities relating to the oversight of our investment in pharmaceutical R&D. In furtherance of that oversight function, the S&T committee:

	reviews and assesses our current and planned R&D programs and technology initiatives from a scientific perspective;
	oversees risks related to our R&D investments;
	assesses the depth and breadth of our scientific personnel and resources; and
	provides strategic advice to our board regarding emerging science and technology issues and trends.

Compensation Committee Interlocks and Insider Participation

Messrs. Carney, Kearney, Lee, and Sachs, Ms. McKenzie and Mr. Yuchun Lee, a former member of our board of directors, served on the MDCC during 2022.2023. Each member of the MDCC was an independent director while serving on the MDCC. None of the members of the MDCC has been an officer or employee of the company. None of the members of our MDCC had a relationship with the company or any of its subsidiaries during 20222023 that would be required to be disclosed pursuant to Item 404(a) of Regulation S-K. During 2022,2023, none of our executive officers served as a member of the board of directors or compensation committee of another company that has one or more executive officers serving as a member of our board or MDCC.

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Board Attendance, Committee Meetings, and Committee Membership

During 2022,2023, our board of directors met seven5 times. Each of our incumbent directors attended 100%at least 75% of the total meetings of the board and the board committees on which the director served that were held during the time that person was a director in 2022.2023. All of our current directors attended our 2022 Annual Meeting2023 annual meeting of Shareholders.shareholders.

The following table provides information regarding our current board of directors. Jennifer Schneider has been nominated for our board of directors and therefore is not included in the table below. We expect that in May 2023, (i) Mr. Carney will join the Corporate Governance and Nominating Committee as Chair, and (ii) we will make additional changes later this year to our committee memberships resulting from the departuresdeparture of Mr. Lee and Ms. McGlynnKearney following the 2023 Annual Meeting2024 annual meeting of Shareholders.shareholders.

Director

Independence

Board

Audit Committee

CGNC

MDCC

S&T Committee

Independence

Board

Audit Committee

CGNC

MDCC

S&T Committee

Sangeeta N. Bhatia

Lloyd Carney

Alan Garber

Terrence C. Kearney

Reshma Kewalramani

Yuchun Lee

Michel Lagarde

Jeffrey M. Leiden

Margaret G. McGlynn

Diana McKenzie

Bruce I. Sachs

Nancy Thornberry

Suketu Upadhyay

2022 Meetings

7

8

5

6

5

2023 Meetings

5

7

5

5

4

	= Member
	= Chair
	= Lead Independent Director

Risk Management

Our board oversees an enterprise-wide approach to risk management, which is designed to support execution of our strategy and achievement of our goals to improve long-term operational and financial performance and generate long-term value for our shareholders. Our board believes that a fundamental part of risk management is understanding the risks that we face, adopting appropriate controls and mitigation activities for such risks, monitoring these risks, and responding to emerging developments with respect to such risks.

In performing its risk oversight responsibilities, the board relies, in part, upon the results and information gained through our annual Enterprise Risk Management (“ERM”) Program. The ERM Program is overseen by our Chief Risk & Compliance Officer, who reports to our Chief Legal Officer, and is designed to identify key enterprise risks and ensure appropriate monitoring of, and controls over, those risks. As part of our ERM Program, we obtain input from our senior management and relevant subject-matter experts, evaluate industry trends and benchmarks, and consult external advisors as appropriate to identify the risks associated with our business based on likelihood of occurrence and potential impact to the business, as well as root causes of those risks. The ERM Program also assigns members of management responsibility for implementing controls and mitigations to reduce the likelihood or impact of each risk. The identified risks and related controls and mitigations are actively monitored by the board and regularly reviewed with senior management.

The board’s role in our risk management process also includes reviewing regular reports and updates from senior management on both near-term, medium-term and long-term risks to the company. The board reviews and discusses strategic, operational, financial, compliance, legal, social (e.g., human capital management), environmental, governance, cybersecurity, and other risks. The board also receives updates from management regarding various enterprise risks related to our research, development, and commercialization plans, such as the competitive environment, manufacturing capabilities, product safety and quality, and drug pricing and reimbursement. These activities enable the board to understand and assess our risk environment, risk management, and risk mitigation strategies.

Near- and medium-term enterprise risks are afforded significant attention by the board. The board and its committees have the opportunity to provide input and direction as to the management of those risks in a variety of manners, including through the ERM Program review, regular operational and financial updates and review of development programs, regular updates from our Chief Legal Officer, internal audit updates, talent reviews and succession planning, updates on cyber-security, healthcare compliance updates, reviews of executive compensation, budget

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reviews, and reviews of significant transactions. Longer term risks are addressed by the board through the annual strategic planning process, during which the board discusses and reviews our long-term operating plans and overall corporate strategy. Other risks that do not rise to the level of enterprise risks also are regularly assessed, discussed, managed, and monitored, including discussion with the board, as appropriate.

Cross-functional members of management, including from our finance, accounting, investor relations, legal, compliance, information security, facilities, corporate communications, manufacturing, and disease strategy teams, work to ensure that material incidents and risks, including matters relating to significant actual or threatened litigation, significant regulatory matters and other matters that may have material financial, legal or reputational impacts on the Companycompany are timely reported to the Boardboard and senior management and disclosed to our shareholders, as appropriate. In addition, we disclose our significant environmental, social and governance progress, strategies, and commitments in our annual Corporate Responsibility Report.

While the board has the ultimate oversight responsibility for risk management, the board also manages risk through the division of responsibility within its committee structure, with each board committee being responsible for overseeing risk within its area of focus.

At each regular meeting, or more frequently as needed, the board receives and considers committee reports, and such reports may provide additional detail on risk management issues and management’s response. The board and each committee also have the authority, in their sole discretion, to consult with and retain outside advisors and experts in connection with performance of its duties and responsibilities. Such outside advisors and experts are retained on a regular basis to assist the board and its committees in evaluating, managing, and anticipating risks, and include external auditors, legal counsel, compensation consultants, and business consultants, as appropriate. We have also established robust standards of business conduct that apply to all employees globally and provides numerous methods for employees to elevate risk concerns directly to management or through anonymous channels.

Code of Conduct

We have adopted a Code of Conduct that applies to all of our directors and employees, including our CEO and chief financial and accounting officers. We routinely review our Code of Conduct and make updates, as necessary. Our Code of Conduct is available on our website www.vrtx.com under “Investors—Corporate Governance—Governance Documents.” Disclosure regarding any amendments to, or waivers from, provisions of the Code of Conduct that apply to our principal executive, financial or accounting officers, or controller or persons performing similar functions will be posted on our website or included in a Current Report on Form 8-K within four business days following the date of the amendment or waiver.

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